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Biotech / Medical : Biotransplant(BTRN) -- Ignore unavailable to you. Want to Upgrade?

To: sim1 who wrote (619)	8/2/2000 9:45:37 PM
From: scaram(o)uche	Respond to of 1475

Very interesting. I don't know if CTLA4-Ig blocks recognition of the pocine molecule (CD86) by human T cells. Cool work. However..... active immunization to induce a blocking antibody for "significantly prolonged survival" in a mouse model?...... don't hold your breath. Just parking (not directly relevant, but full of very interesting stuff)........ J Clin Invest 2000 Jul;106(1):63-72 The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivo. Kishimoto K, Dong VM, Issazadeh S, Fedoseyeva EV, Waaga AM, Yamada A, Sho M, Benichou G, Auchincloss H Jr, Grusby MJ, Khoury SJ, Sayegh MH Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. We used signal transducer and activator of transcription 4 (STAT4) and STAT6 gene knockout (-/-) mice as recipients of fully mismatched cardiac allografts to study the role of T-cell costimulatory pathways in regulating allogeneic T-helper 1 (Th1) versus Th2 responses in vivo. STAT4(-/-) mice have impaired Th1 responses, whereas STAT6(-/-) mice do not generate normal Th2 responses. Cardiac allografts from C57BL/6 mice were transplanted into normal wild-type (WT), STAT4(-/-), and STAT6(-/-) BALB/c recipients. STAT4(-/-) and STAT6(-/-) mice rejected their grafts with the same tempo as untreated WT recipients. CD28-B7 blockade by a single injection of CTLA4Ig induced long-term engraftment and donor-specific tolerance in all three groups of recipients. CD154 blockade by a single injection of MR1 was effective in prolonging allograft survival and inducing tolerance in STAT4(-/-) mice but was only marginally effective in STAT6(-/-) recipients and WT controls. In addition, a similar protocol of MR1 was ineffective in prolonging graft survival in CD28(-/-) BALB/c recipients, suggesting that the lack of efficacy seen in WT and STAT6(-/-) mice is not due to the presence of a functional CD28-B7 pathway. Furthermore, there was a similar differential effect of CD28-B7 versus CD154-CD40 blockade in inhibiting immune responses in animals immunized with ovalbumin and complete Freund's adjuvant. These novel data indicate that Th1 and Th2 cells are differentially regulated by CD28-B7 versus CD154-CD40 costimulation pathways in vivo and may have potential implications for the development of therapeutic strategies such as T-cell costimulatory blockade in humans.